U.S. Pat. No. 3,635,986 (issued Jan. 18, 1972) discloses 2-substituted amino-hexahydrobenzo [a] quinolizines of the formula: ##STR3## wherein R and R' can be H or O-(lower) alkyl, R.sup.6 can be H and R.sup.3 can be substituted phenyl. This reference does not disclose substitution of the phenyl ring (when R.sup.3 is phenyl) with an amine or amide group.
U.S. Pat. No. 3,995,041 (issued Nov. 30, 1976) discloses derivatives of 2-substituted-hydroxyanilino-hexahydro-2H-benzo [a] quinolizines of the formula: ##STR4## wherein R.sup.1 is hydrogen or an alkanoyl group of 2 to 4 carbon atoms and R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are hydrogen, hydroxyl or methyl with the proviso that at least one of the R.sup.2 -R.sup.6 groups is hydroxyl.
These prior art compounds are disclosed as having utility as anti-hypertensive agents and coronary dilators respectively.
The compounds of the present invention differ from those of the prior art in that the anilino group in the molecule is p-substituted with an amide group. The compounds of this invention exhibit utility as anti-hypertensive agents. In addition, certain of the compounds disclosed herein, in contrast to prior art compounds of similar chemical structure, exhibit the ability to lower blood pressure without producing tachycardia.
Compounds lowering blood pressure by producing peripheral vasodilatation, such as hydralazine, have found limited use in the treatment of arterial hypertension mainly because their blood pressure effect is accompanied by reflex cardiac stimulation (D. M. Aviado and H. Salem, in New Antihypertensive Drugs, A. Scriabine and C. S. Sweet, eds. Spectrum Publications, New York, 1975. p. 527). Benzoquinolizine derivatives have been reported to decrease blood pressure by this mechanism (J. W. Van Dyke et al. J. Med. Chem. 15:91, 1972). Some of the present compounds elicit this effect without producing concomitant cardiac stimulation, as evidenced by their lack of effect on heart rate.